In this paper, we show that neonatal mice injected for five consecutive days with nicotine display impaired germ cell cyst breakdown and primordial follicle assembly resulting in decreased ovarian reserve lasting until sex maturation age. The effects of nicotine on the pups ovaries were associated with decreased expression of oocyte specific genes such as Nobox, Lhx8, Figlα and Sohlh2. Moreover, the ovaries of pups injected with nicotine showed increased level of cell oxidative stress and autophagic markers (upregulation of AMPKα-1, increased ratio LC3-II/LC3-I, downregulation of AKT and mTOR). Noteworthy, all these effects were counteracted by the administration of the hormone melatonin in 1 μM. In vitro culture of 0 dpp ovaries for 5 days in the presence of 10 μM nicotine reproduced its effect on germ cell cyst breakdown and primordial follicle assembly, furthermore it also revealing about 20% reduction of somatic cells proliferation, and these effects was prevented when melatonin was added to the medium. Taken together these results show that nicotine exposure can adversely affect the establishment of the ovarian reserve in the mouse likely by locally inducing cellular stress altering the primordial follicle assembly and that melatonin, however, is able to counteract such effects.
BackgroundIn treating juvenile-onset laryngeal papillomatosis, the most difficult aspect is preventing recurrence. After a single treatment, recurrence can begin after as soon as 20 days and the recurrent rate can be higher than 90%. The causes of recurrence include the presence of mucosal cells infected with papilloma virus, which are undetectable with the naked eyes, and surgery-induced infection. Photodynamic therapy (PDT) could effectively solve this problem. Virus-infected cells have a very high metabolic energy for capturing and internalizing the photosensitizer, which, after light stimulation, subsequently induces active oxygen species inside the nucleus, which kill infected cells. The second generation of photosensitizer agents (PA) are locally applied to avoid the intravenous systemic damage caused by first-generation PAs, and this method is widely used for the treatment of genital warts to very good effect.MethodsWe used the photodynamic method to treat laryngeal papillomatosis in children and obtained significant efficacy. We followed three juvenile subjects with recurrent laryngeal papillomatosis through a course of treatment (each course includes three PDT sessions), with a follow-up after 6 months.ResultsThe characteristic procedures involve exposing the larynx with a laryngoscope and using low-temperature plasma technology to visualize the tumor resection, as the effects of plasma technology can reduce postoperative laryngeal edema and reduce intraoperative metastasis. PDT was performed during the first surgery, 20 days after and 30 days after surgery. At the 6-month follow-ups, there was no recurrence.ConclusionThis was the world's first successful reported case of the use of PDT treatment for juvenile laryngeal papillomatosis.
In the present paper, we found that human fetal ovaries (at ~16 weeks) express the transcripts for several subunits of the nicotinic acetylcholine receptor (nAChR). Exposure to the drug in vitro resulted in the marked increase of apoptosis in the ovaries in a time and dose-dependent manner. Evidence that adverse nicotine effects are potentially due to an increased level of reactive oxygen species (ROS) and consequent DNA damage, both in the ovarian somatic cells and germ cells, are reported. After 4 days of culture, exposure to 1 mM and 10 mM nicotine caused a 50% and 75% decrease, respectively, in the number of oogonia/oocytes present in the fetal ovaries. These results represent the first indication that nicotine may directly cause apoptosis in cells of the fetal human ovary and may lead to a reduction of the ovarian reserve oocytes and consequent precocious menopause in mothers smoking during pregnancy.
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